Although several full length proviral DNAs capable of producing infectious Simian Immune Deficiency virus (SIV) have been isolated, none of the virus strains so produced induce a typical SIV related immune deficiency syndrome in monkeys. The goal of this proposal is to produce a cloned SIV provirus that yields virus which initiates infection and induces typical SIV associated immunologic and central nervous system disease in Rhesus monkeys. Approaches to be taken include isolation of proviral DNA from primary lymphocytes and bone marrow cells of Rhesus monkeys in the early stages of disease, and isolation of an SIVmac251 provirus capable of producing all known SIV encoded proteins. The role of nef and vif of SIVmac251 in initiation of infection will also be investigated. Objectives include: 1. Isolation of 20-30 full-length proviral DNAs from lymphocytes and from macrophages of Rhesus monkeys in the early stage of SIV induced disease. Isolation of 20-30 full-length proviral DNAs from a lymph node tissue from the monkey from which SIVmac251 was originally isolated. Creation of an infectious "consensus" SlVmac251 provirus. 2. Test of the ability of the provirus to produce virus capable of infecting primary cultures of Rhesus lymphocytes and bone marrow macrophages. 3. Test of the ability of three lymphocyte isolates, three bone marrow isolates, one lymph node isolate, and one "consensus" virus isolate to infect and to induce typical SIV disease in Rhesus monkeys. 4. Investigation of difference in the initial growth rate, state of chronic viremia and level of anti-SIV antibodies of viruses isogeneic except for nef and vif. This proposal combines the skills of Dr. William Haseltine, a molecular biologist and virologist, with those of Dr. Norman Letvin, an immunologist and specialist in SIV disease.